Lipid-Based Nanocarriers for Neurological Disorders: A Review of the State-of-the-Art and Therapeutic Success to Date

Abstract

Neurodegenerative disorders including Alzheimer’s, Parkinson’s, and dementia are chronic and advanced diseases that are associated with loss of neurons and other related pathologies. Furthermore, these disorders involve structural and functional defections of the blood–brain barrier (BBB). Consequently, advances in medicines and therapeutics have led to a better appreciation of various pathways associated with the development of neurodegenerative disorders, thus focusing on drug discovery and research for targeted drug therapy to the central nervous system (CNS). Although the BBB functions as a shield to prevent toxins in the blood from reaching the brain, drug delivery to the CNS is hindered by its presence. Owing to this, various formulation approaches, including the use of lipid-based nanocarriers, have been proposed to address shortcomings related to BBB permeation in CNS-targeted therapy, thus showing the potential of these carriers for translation into clinical use. Nevertheless, to date, none of these nanocarriers has been granted market authorization following the successful completion of all stages of clinical trials. While the aforementioned benefits of using lipid-based carriers underscores the need to fast-track their translational development into clinical practice, technological advances need to be initiated to achieve appropriate capacity for scale-up and the production of affordable dosage forms.

CRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson’s Disease

“…For nucleic acid delivery, lipid-based nanoparticles (LNPs) are often used [291]. As LNPs address BBB permeation well, they are widely developed for CNS-targeted therapy [292]. Liposomes are perfectly circular lipid bilayer entities that form in an aqueous solution.…”

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders

“…It regulates molecular exchange pathways that transport molecules from blood to brain and brain to blood [ 13 ]. It separates peripheral circulation from the CNS, thereby protecting the brain from unwanted molecules and foreign substances allowing only the exchange of small molecules that are permeable to the BBB into the brain by diffusion [ 5 , 14 ]. Unfortunately, the BBB along with the presence of the blood-cerebrospinal fluid barrier and efflux transporters presents a huge challenge for the effective delivery of therapeutics to the CNS [ 14 , 15 ].…”

“…The prevalence of neurodegenerative diseases presents a major threat to the health of the elderly population. Parkinson’s disease, for example, causes disabling symptoms such as tremors, muscle stiffness, and postural instability, which can cause falls resulting in further debilitation [ 4 , 5 ]. Alzheimer’s disease, on the other hand, causes memory and cognitive impairments, while ALS affects basic motor neuron functions such as speaking, swallowing, and breathing [ 3 , 6 ].…”

“…Alzheimer’s disease, on the other hand, causes memory and cognitive impairments, while ALS affects basic motor neuron functions such as speaking, swallowing, and breathing [ 3 , 6 ]. Chronic CNS disorders such as epilepsy and schizophrenia require long-term drug therapy to control symptoms [ 5 , 7 ].…”

“…The treatment of these neurological disorders is mainly hindered by the blood-brain barrier (BBB), whose physiological function is to regulate the transport of substances to the brain and prevent the entry of foreign substances that could damage it [ 8 ], resulting in inadequate drug concentrations reaching neuronal tissues [ 5 ]. In the clinical setting, attempts to circumvent BBB effects on CNS drugs often include elevation of doses or frequent dosing intervals.…”